Acknowledgement
Department of Innovative Biomedical Visualization (iBMV), Nagoya University is supported by CANON MEDICAL SYSTEMS CORPORATION.
References
- Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest 2013;123:1299-1309 https://doi.org/10.1172/JCI67677
- Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012;4:147ra111
- Agarwal N, Contarino C, Toro EF. Neurofluids: a holistic approach to their physiology, interactive dynamics and clinical implications for neurological diseases. Veins and Lymphatics 2019;8:49-58 https://doi.org/10.4081/vl.2019.8470
- Taoka T, Naganawa S. Glymphatic imaging using MRI. J Magn Reson Imaging 2020;51:11-24 https://doi.org/10.1002/jmri.26892
- Cushing H. Cameron lecture. Lancet 1925;206:851-857 https://doi.org/10.1016/S0140-6736(01)17422-2
- Weed LH. Studies on cerebro-spinal fluid. no. III: the pathways of escape from the subarachnoid spaces with particular reference to the arachnoid villi. J Med Res 1914;31:51-91
- Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis 2011;128:309-316 https://doi.org/10.1016/j.anorl.2011.03.002
- Oreskovic' D, Klarica M. The formation of cerebrospinal fluid: nearly a hundred years of interpretations and misinterpretations. Brain Res Rev 2010;64:241-262 https://doi.org/10.1016/j.brainresrev.2010.04.006
- Carare RO, Hawkes CA, Weller RO. Afferent and efferent immunological pathways of the brain. Anatomy, function and failure. Brain Behav Immun 2014;36:9-14 https://doi.org/10.1016/j.bbi.2013.10.012
- Miyajima M, Arai H. Evaluation of the production and absorption of cerebrospinal fluid. Neurol Med Chir (Tokyo) 2015;55:647-656 https://doi.org/10.2176/nmc.ra.2015-0003
- Kida S, Pantazis A, Weller RO. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 1993;19:480-488 https://doi.org/10.1111/j.1365-2990.1993.tb00476.x
- Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res 2004;1:2
- Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today 1992;13:507-512 https://doi.org/10.1016/0167-5699(92)90027-5
- Mollanji R, Bozanovic-Sosic R, Silver I, Li B, Kim C, Midha R, et al. Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics. Am J Physiol Regul Integr Comp Physiol 2001;280:R1573-R1581 https://doi.org/10.1152/ajpregu.2001.280.5.R1573
- Nedergaard M, Goldman SA. Brain drain. Sci Am 2016;314:44-49 https://doi.org/10.1038/scientificamerican0316-44
- Schley D, Carare-Nnadi R, Please CP, Perry VH, Weller RO. Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol 2006;238:962-974 https://doi.org/10.1016/j.jtbi.2005.07.005
- Asgari M, de Zelicourt D, Kurtcuoglu V. Glymphatic solute transport does not require bulk flow. Sci Rep 2016;6:38635
- Jin BJ, Smith AJ, Verkman AS. Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism. J Gen Physiol 2016;148:489-501 https://doi.org/10.1085/jgp.201611684
- Spector R, Snodgrass SR, Johanson CE. A balanced view of the cerebrospinal fluid composition and functions: focus on adult humans. Exp Neurol 2015;273:57-68 https://doi.org/10.1016/j.expneurol.2015.07.027
- Kanda T. The new restrictions on the use of linear gadolinium-based contrast agents in Japan. Magn Reson Med Sci 2019;18:1-3 https://doi.org/10.2463/mrms.e.2017-0176
- Taoka T, Naganawa S. Gadolinium-based contrast media, cerebrospinal fluid and the glymphatic system: possible mechanisms for the deposition of gadolinium in the brain. Magn Reson Med Sci 2018;17:111-119 https://doi.org/10.2463/mrms.rev.2017-0116
- Naganawa S, Taoka T, Kawai H, Yamazaki M, Suzuki K. Appearance of the organum vasculosum of the lamina terminalis on contrast-enhanced MR imaging. Magn Reson Med Sci 2018;17:132-137 https://doi.org/10.2463/mrms.mp.2017-0088
- Samardzic D, Thamburaj K. Magnetic resonance characteristics and susceptibility weighted imaging of the brain in gadolinium encephalopathy. J Neuroimaging 2015;25:136-139 https://doi.org/10.1111/jon.12067
- Eide PK, Ringstad G. MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain. Acta Radiol Open 2015;4:2058460115609635
- Oner AY, Barutcu B, Aykol S, Tali ET. Intrathecal contrast-enhanced magnetic resonance imaging-related brain signal changes: residual gadolinium deposition? Invest Radiol 2017;52:195-197 https://doi.org/10.1097/RLI.0000000000000327
- Ringstad G, Valnes LM, Dale AM, Pripp AH, Vatnehol SS, Emblem KE, et al. Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. JCI Insight 2018;3:e121537
- Ringstad G, Vatnehol SAS, Eide PK. Glymphatic MRI in idiopathic normal pressure hydrocephalus. Brain 2017;140:2691-2705 https://doi.org/10.1093/brain/awx191
- Zhou Y, Cai J, Zhang W, Gong X, Yan S, Zhang K, et al. Impairment of the glymphatic pathway and putative meningeal lymphatic vessels in the aging human. Ann Neurol 2020;87:357-369 https://doi.org/10.1002/ana.25670
- Edeklev CS, Halvorsen M, Lovland G, Vatnehol SAS, Gjertsen O, Nedregaard B, et al. Intrathecal use of gadobutrol for glymphatic MR imaging: prospective safety study of 100 patients. AJNR Am J Neuroradiol 2019;40:1257-1264 https://doi.org/10.3174/ajnr.A6136
- van de Haar HJ, Burgmans S, Jansen JF, van Osch MJ, van Buchem MA, Muller M, et al. Blood-brain barrier leakage in patients with early Alzheimer disease. Radiology 2016;281:527-535 https://doi.org/10.1148/radiol.2016152244
- Li Y, Li M, Yang L, Qin W, Yang S, Yuan J, et al. The relationship between blood-brain barrier permeability and enlarged perivascular spaces: a cross-sectional study. Clin Interv Aging 2019;14:871-878 https://doi.org/10.2147/CIA.S204269
- Huber VJ, Igarashi H, Ueki S, Kwee IL, Nakada T. Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study. Neuroreport 2018;29:697-703 https://doi.org/10.1097/WNR.0000000000000990
- Naganawa S, Suzuki K, Yamazaki M, Sakurai Y. Serial scans in healthy volunteers following intravenous administration of gadoteridol: time course of contrast enhancement in various cranial fluid spaces. Magn Reson Med Sci 2014;13:7-13 https://doi.org/10.2463/mrms.2013-0056
- Naganawa S, Nakane T, Kawai H, Taoka T. Gd-based contrast enhancement of the perivascular spaces in the basal ganglia. Magn Reson Med Sci 2017;16:61-65 https://doi.org/10.2463/mrms.mp.2016-0039
- Naganawa S, Nakane T, Kawai H, Taoka T. Lack of contrast enhancement in a giant perivascular space of the basal ganglion on delayed flair images: implications for the glymphatic system. Magn Reson Med Sci 2017;16:89-90 https://doi.org/10.2463/mrms.ci.2016-0114
- Ohashi T, Naganawa S, Katagiri T, Kuno K. Relationship between contrast enhancement of the perivascular space in the basal ganglia and endolymphatic volume ratio. Magn Reson Med Sci 2018;17:67-72 https://doi.org/10.2463/mrms.mp.2017-0001
- Naganawa S, Nakane T, Kawai H, Taoka T. Differences in signal intensity and enhancement on MR images of the perivascular spaces in the basal ganglia versus those in white matter. Magn Reson Med Sci 2018;17:301-307 https://doi.org/10.2463/mrms.mp.2017-0137
- Ohashi T, Naganawa S, Ogawa E, Katagiri T, Kuno K. Signal intensity of the cerebrospinal fluid after intravenous administration of gadolinium-based contrast agents: strong contrast enhancement around the vein of labbe. Magn Reson Med Sci 2019;18:194-199 https://doi.org/10.2463/mrms.mp.2018-0043
- Naganawa S, Nakane T, Kawai H, Taoka T. Age dependence of gadolinium leakage from the cortical veins into the cerebrospinal fluid assessed with whole brain 3D-real inversion recovery MR imaging. Magn Reson Med Sci 2019;18:163-169 https://doi.org/10.2463/mrms.mp.2018-0053
- Naganawa S, Ito R, Taoka T, Yoshida T, Sone M. The space between the pial sheath and the cortical venous wall may connect to the meningeal lymphatics. Magn Reson Med Sci 2020;19:1-4 https://doi.org/10.2463/mrms.bc.2019-0099
- Taoka T, Masutani Y, Kawai H, Nakane T, Matsuoka K, Yasuno F, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases. Jpn J Radiol 2017;35:172-178 https://doi.org/10.1007/s11604-017-0617-z
- Demiral SB, Tomasi D, Sarlls J, Lee H, Wiers CE, Zehra A, et al. Apparent diffusion coefficient changes in human brain during sleep-does it inform on the existence of a glymphatic system? Neuroimage 2019;185:263-273 https://doi.org/10.1016/j.neuroimage.2018.10.043
- Wong SM, Backes WH, Drenthen GS, Zhang CE, Voorter PHM, Staals J, et al. Spectral diffusion analysis of intravoxel incoherent motion MRI in cerebral small vessel disease. J Magn Reson Imaging 2020;51:1170-1180 https://doi.org/10.1002/jmri.26920
- Taoka T, Naganawa S, Kawai H, Nakane T, Murata K. Can low b value diffusion weighted imaging evaluate the character of cerebrospinal fluid dynamics? Jpn J Radiol 2019;37:135-144 https://doi.org/10.1007/s11604-018-0790-8
- Ohene Y, Harrison IF, Nahavandi P, Ismail O, Bird EV, Ottersen OP, et al. Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study. Neuroimage 2019;188:515-523 https://doi.org/10.1016/j.neuroimage.2018.12.026
- Yamada S, Miyazaki M, Kanazawa H, Higashi M, Morohoshi Y, Bluml S, et al. Visualization of cerebrospinal fluid movement with spin labeling at MR imaging: preliminary results in normal and pathophysiologic conditions. Radiology 2008;249:644-652 https://doi.org/10.1148/radiol.2492071985
- Yatsushiro S, Sunohara S, Hayashi N, Hirayama A, Matsumae M, Atsumi H, et al. Cardiac-driven pulsatile motion of intracranial cerebrospinal fluid visualized based on a correlation mapping technique. Magn Reson Med Sci 2018;17:151-160 https://doi.org/10.2463/mrms.mp.2017-0014
- Takizawa K, Matsumae M, Hayashi N, Hirayama A, Sano F, Yatsushiro S, et al. The choroid plexus of the lateral ventricle as the origin of CSF pulsation is questionable. Neurol Med Chir (Tokyo) 2018;58:23-31 https://doi.org/10.2176/nmc.oa.2017-0117
- Raz E, Dehkharghani S, Shapiro M, Nossek E, Jain R, Zhang C, et al. Possible empirical evidence of glymphatic system on computed tomography after endovascular perforations. World Neurosurg 2020;134:e400-e404 https://doi.org/10.1016/j.wneu.2019.10.089
- Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science 2013;342:373-377 https://doi.org/10.1126/science.1241224
- Lee H, Xie L, Yu M, Kang H, Feng T, Deane R, et al. The effect of body posture on brain glymphatic transport. J Neurosci 2015;35:11034-11044 https://doi.org/10.1523/JNEUROSCI.1625-15.2015
- Matsuda H, Shigemoto Y, Sato N. Neuroimaging of Alzheimer's disease: focus on amyloid and tau PET. Jpn J Radiol 2019;37:735-749 https://doi.org/10.1007/s11604-019-00867-7
- McKee AC, Cairns NJ, Dickson DW, Folkerth RD, Keene CD, Litvan I, et al. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 2016;131:75-86 https://doi.org/10.1007/s00401-015-1515-z
- Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, et al. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci 2014;34:16180-16193 https://doi.org/10.1523/JNEUROSCI.3020-14.2014
- Inglese M, Bomsztyk E, Gonen O, Mannon LJ, Grossman RI, Rusinek H. Dilated perivascular spaces: hallmarks of mild traumatic brain injury. AJNR Am J Neuroradiol 2005;26:719-724
- Yokota H, Vijayasarathi A, Cekic M, Hirata Y, Linetsky M, Ho M, et al. Diagnostic performance of glymphatic system evaluation using diffusion tensor imaging in idiopathic normal pressure hydrocephalus and mimickers. Curr Gerontol Geriatr Res 2019;2019:5675014
- Mestre H, Kostrikov S, Mehta RI, Nedergaard M. Perivascular spaces, glymphatic dysfunction, and small vessel disease. Clin Sci (Lond) 2017;131:2257-2274 https://doi.org/10.1042/CS20160381
- Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E, et al. Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease. Neurobiol Dis 2016;93:215-225 https://doi.org/10.1016/j.nbd.2016.05.015
- Gaberel T, Gakuba C, Goulay R, De Lizarrondo SM, Hanouz JL, Emery E, et al. Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis? Stroke 2014;45:3092-3096 https://doi.org/10.1161/STROKEAHA.114.006617
- Pu T, Zou W, Feng W, Zhang Y, Wang L, Wang H, et al. Persistent malfunction of glymphatic and meningeal lymphatic drainage in a mouse model of subarachnoid hemorrhage. Exp Neurobiol 2019;28:104-118 https://doi.org/10.5607/en.2019.28.1.104
- Jiang Q, Zhang L, Ding G, Davoodi-Bojd E, Li Q, Li L, et al. Impairment of the glymphatic system after diabetes. J Cereb Blood Flow Metab 2017;37:1326-1337 https://doi.org/10.1177/0271678X16654702
- Sato O, Asai T, Amano Y, Hara M, Tsugane R, Yagi M. Formation of cerebrospinal fluid in spinal subarachnoid space. Nature 1971;233:129-130 https://doi.org/10.1038/233129a0
- Ohata K, Marmarou A, Povlishock JT. An immunocytochemical study of protein clearance in brain infusion edema. Acta Neuropathol 1990;81:162-177 https://doi.org/10.1007/BF00334505